Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis

Draube, Andreas; Klein-González, Nela; Mattheus, Stefanie; Brillant, Corinne; Hellmich, Martin; Engert, Andreas; Bergwelt‐Baildon, Michael von

doi:10.1371/journal.pone.0018801

Cited by 194 publications

(162 citation statements)

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“…Side effects seen with the majority of DC vaccination protocols were minimal and selflimiting, mainly including flu-like symptoms, fever, and local reactions at the injection site. Grade 3 or 4 treatment-related toxicity is extremely uncommon when DC vaccination is given as monotherapy (15). These data are confirmed by the available data from phase III trials where DC vaccination is compared with placebo (16)(17)(18)(19).…”

Section: Safetymentioning

confidence: 68%

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Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

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Schreibelt

Gerritsen

et al. 2016

Clinical Cancer Research

312

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Dendritic cell (DC) vaccination in cancer patients aims to induce or augment an effective antitumor immune response against tumor antigens and was first explored in a clinical trial in the 1990s. More than two decades later, numerous clinical trials have been performed or are ongoing with a wide variety of DC subsets, culture protocols, and treatment regimens. The safety of DC vaccination and its ability to induce antitumor responses have clearly been established; however, although scattered patients with long-term benefit were reported, DC vaccines have not yet fulfilled their promise, perhaps mainly due to the lack of large-scale well-conducted phase II/III trials. To allow meaningful multicenter phase III trials, the production of DC vaccines should be standardized between centers which is now becoming feasible. To improve the efficacy of DC-based immunotherapy, it could be combined with other treatments.

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Section: Safetymentioning

confidence: 68%

“…Later trials demonstrated superiority of mature DCs over their immature counterparts in terms of the immunogenicity and clinical outcome (15,(20)(21)(22). Besides their enhanced migratory capacity (23), mature DCs also have a higher expression of MHC and costimulatory molecules.…”

Section: Maturation Of Dcsmentioning

confidence: 99%

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Bol

Schreibelt

Gerritsen

et al. 2016

Clinical Cancer Research

312

245

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“…Clinical responses to vaccine were evaluated according to the World Health Organization criteria (18): complete response was defined as complete disappearance of tumor, partial response was defined as ≥50% reduction in the product of two longest perpendicular diameters of tumor without the appearance of new metastases, stable disease was defined as <50% decrease to <25% increase in tumor size, and progressive disease was defined as ≥25% increase in tumor size or the appearance of new metastases. Among the 166 patients who finished therapy, 77 (46%) had clinical response with 6 complete responses, 13 partial responses, and 58 disease stabilizations (17). Treatment with dendritic cell-based vaccine was only accompanied by mild adverse effects such as local reactions at the injection site, flu-like symptoms, and fever.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody enhances antitumor efficacy in renal cell carcinoma-bearing mice

et al. 2017

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IntroductionRenal cell carcinoma accounts for 4% of all malignant tumors (1) and has an incidence of about 8-9 persons per 100,000 each year, which is increasing (2). There is no obvious symptom in the early stage of this cancer. As a result, approximately 25%-30% of patients exhibit tumor metastasis at first diagnosis and lose the opportunity for surgery (3). Although patients with primarily localized renal cell carcinoma can be successfully treated by partial or radical nephrectomy, one third of cases will subsequently develop metastases (4,5). Therapy of metastatic renal cell carcinoma is particularly difficult because of its poor response to radiotherapy or chemotherapy. Therefore, the prognosis for patients with metastatic renal cell carcinoma is poor, and the survival rate for 5 years is less than 10% (6). These lead to a rising demand for other treatment modalities.Prospective studies note spontaneous regression rates of up to 7% in patients with metastatic renal cell carcinoma (7,8). In addition, immunohistochemical studies of renal cell carcinoma often reveal tumor-infiltrating dendritic cells and T lymphocytes able to recognize and kill tumor cells (9). Therefore, renal cell carcinoma is considered an immunogenic tumor. These findings also lead to attempts to develop immunotherapeutic strategies using immunostimulatory cytokines such as interleukin-2 and interferon-α (10). It has been reported that treatment with interleukin-2 and interferon-α can induce antitumor activity in less than 20% of patients with metastatic renal cell carcinoma, but is associated with a high incidence Background/aim: Dendritic cell-based vaccine therapy for renal cell carcinoma is effective but requires improvement. Here we explored whether combination therapy with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor efficacy in renal cell carcinoma-bearing mice.Materials and methods: Balb/c mice were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated or were treated with Renca tumor lysate-pulsed dendritic cells (i.e. dendritic cell-based vaccine), anti-CD69 antibody, or a combination of Renca tumor lysate-pulsed dendritic cells with anti-CD69 antibody. The mice were sacrificed on day 28. Tumor volume was measured for analysis of antitumor efficacy. Spleens were excised to evaluate antitumor immunological responses by measuring the proliferation and activation of T cells, which have the capacity to recognize and destroy tumor cells.Results: Combination treatment with Renca tumor lysate-pulsed dendritic cells and anti-CD69 antibody resulted in significant decreases in tumor volume and significant increases in T-cell proliferation and activity, compared with no treatment or either treatment alone. Conclusion:These findings indicate that anti-CD69 antibody can potentiate antitumor efficacy of dendritic cell-based vaccine. The augmented therapeutic efficacy conferred by the combination therapy may be as...

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“…44 Another promising new approach is adoptive cell therapy using engineered T-cell Chimeric Antigen Receptor (CAR). 45 Clinical trial results for therapeutic RCC vaccines We reviewed 6 clinical trials of RCC-specific therapeutic vaccines administered in an adjuvant or a metastatic setting: three completed phase III trials (Reniale, [46][47] Trovax, [48][49][50] and Vitespen 51 ) and three phase II trials (TG4010, 52 AGS003, [53][54] and IMA901 21 ), as well as a meta-analysis of dendritic cell (DC)-based vaccines in mRCC 55 ( Table 1). The publications were retrieved from a Medline search (from january 2004 to november 2014).…”

Section: Immune Escape Mechanisms In Ccrccmentioning

confidence: 99%

“…The cellular immune response and DC dose (mean= 38.7£10*6 cells) were the main predictors of response. 55 …”

Section: Dc-vaccinesmentioning

confidence: 99%